# US 5,344,755 A · Method for detecting immune system dysfunction in asymptomatic, HIV-scropositive individuals

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- Number: US 5,344,755 A
- Document ID: US5344755A
- Status: Granted
- Kind: A
- Application number: 07/535,407
- Filed: 1990-06-08
- Granted: 1994-09-06
- Earliest claimed: 1990-04-21
- Assignees: The United States of America as represented by the Department of Health and Human Services
- Inventors: Gene M. Shearer; Ronald E. Gress; Mario Clerici; Philip J. Lucas; Charles S. Via
- Web page: https://patentgrep.com/patent/US5344755A

## CPC

- G01N 33/56988: {HIV or HTLV}
- G01N 33/56977: {HLA or MHC typing}
- G01N 33/6869: {Interleukin}
- Y10S 435/81: Packaged device or kit
- Y10S 435/974: Aids related test
- Y10S 435/975: Kit
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

A sensitive and accurate tissue culture system and kit for detecting subtle changes in immune function is provided. The system is based on the comparison of IL-2 production by T helper cells in response to recall antigens including influenza A virus, tatanus toxoid, alloantigens, mouse xenogeneic antigens and the like or combinations thereof. Different stages of immune dysfunction can be differentiated and organ graft rejection can be predicted by the method of the present invention.

## Claims

### Claim 1

A method for measuring different stages of immune system dysfunction in asymptomatic, HIV-seropositive individuals comprising:
collecting separated human peripheral blood leukocytes from an individual whose immune system function needs to be measured;
placing a portion of said peripheral blood leukocytes in each of three containers;
exposing the peripheral blood leukocytes in the first container to a first stimulant comprising a recall antigen or a mouse xenogeneic antigen;
exposing the peripheral blood leukocytes in the second container to a second stimulant comprising an alloantigen;
exposing the peripheral blood leukocytes in the third container to a third stimulant comprising a mitogen;
measuring the production of IL-2 by T helper cells in response to each of said three stimulants;
measuring the production of IL-2 by unstimulated peripheral blood leukocytes;
comparing IL-2 production for each of said three stimulants by the T helper cells of the individual whose immune system function needs to be determined to IL-2 production by said unstimulated peripheral blood leukocytes wherein a failure to generate a statistically greater amount of IL-2 is indicative of a failure to respond to that stimulant;
a failure to respond to recall antigens or mouse xenogeneic antigen but responding to alloantigen and mitogen stimulants demonstrating a first level of immune dysfunction of least severity;
a failure to respond to recall antigens or mouse xenogeneic antigen and alloantigens but responding to mitogen stimulant demonstrating a second level of immune dysfunction of intermediate severity;
a failure to respond to recall antigens or mouse xenogeneic antigen, alloantigens, and mitogens demonstrating a third level of immune dysfunction of the greatest severity.

### Claim 2 (depends on 1)

A method of measuring progression to AIDS in asymptomatic, HIV-seropositive individuals comprising measuring the production of IL-2 by the methods of claim 1 wherein a sequential loss in IL-2 production in response first to recall antigens, then to alloantigens, and then to mitogens, over a period of time is predictive of progression to AIDS.

### Claim 3 (depends on 1)

The method of claim 1 in which the first stimulant is mouse xenogeneic antigen.

### Claim 4 (depends on 1)

The method of claim 1 in which the first stimulant is tetanus toxoid.

### Claim 5 (depends on 1)

The method of claim 1 in which the first stimulant is influenza A virus.

### Claim 6 (depends on 1)

The method of claim 1 in which the alloantigens are human peripheral blood leukocytes from any healthy donor who is HLA-mismatched with the person whose immune system function needs to be measured.

### Claim 7 (depends on 1)

The method of claim 1 in which the mitogen is phytohemagglutinin.

### Claim 8

A kit for testing in vitro function of T-helper cells in asymptomatic, HIV-seropositive individuals comprising:
a first T-helper stimulant selected from recall antigens or mouse xenogeneic antigen;
a second T-helper stimulant selected from recall antigens or mouse xenogeneic antigens;
a third T-helper stimulant comprising a mitogen; and
means for measuring IL-2 production of peripheral blood leukocytes in response to said stimulants.

### Claim 9 (depends on 8)

The kit of claim 8 in which said first stimulant is influenza A virus.

### Claim 10 (depends on 8)

The kit of claim 8 wherein said first stimulant is tetanus toxoid.

### Claim 11 (depends on 8)

The kit of claim 8 wherein said first stimulant is mouse xenogeneic antigen.

### Claim 12 (depends on 8)

The kit of claim 8 wherein said third stimulant is phytohemagglutinin.

### Claim 13 (depends on 8)

The kit of claim 8 further comprising the anti-IL-2 receptor antibody, monoclonal anti-TAC.