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Mechanisms of genetic control of immune responses

II. Nonresponsiveness in BALB/c GT-specific cell-mediated immune responses does not correlate with the absence of functional T cells or the induction of suppressor T cells

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Abstract

The mechanisms underlying Ir gene control of CMI were addressed by examining the DTH and Tprlf responses specific for the synthetic polymers GT, GAT, and GA. We show that BALB/c mice (GAT/GA responders, GT nonresponders) primed with GT fail to develop DTH and Tprlf responses specific for GT, GAT, or GA. GAT immunization resulted in DTH responses that could be elicited not only with GAT and GA but also with GT, demonstrating that GT-specific TDH are present in nonresponder mice. GT-specific DTH was transferred with Thy-1+ Lyt-1+2−, H-2 Irestricted, nylon wool nonadherent cells. GA-primed BALB/c mice developed GAT- and GA-, but not GT-apecific DTH responses, indicating that GA and GT do not cross-react at the T-cell level. The ability of GAT [but not a mixture of GA plus GT, or GT electrostatically complexed to the immunogenic carrier MBSA (GT-MBSA)] to induce GT-specific DTH suggested a requirement for covalent linkage of stimulatory ‘GA’ and nonstimulatory ‘GT’ determinants present on the GAT molecule. Similarly, GT-specific in vitro Tprlf responses could be demonstrated in GAT-primed mice exhibiting significant levels of GT-specific DTH but not in GT- or GT-MBSA-primed mice. Tolerization experiments also suggested that GT-specific Th were involved in the development of GT-specific DTH in GAT-primed mice. The GT nonresponsiveness of BALB/c mice for DTH and Tprlf responses could not be reversed by treatments designed to abrogate Ts activity (priming with GT-MBSA and CY injection), nor could GT-primed cells be shown to inhibit the development or elicitation of GT-specific CMI in GAT-primed mice during the afferent and/or efferent stages of DTH. Our results suggest that GT nonresponsiveness does not result from the absence of GT-specific T cells or preferential induction of Ts. The results are discussed in the context of hole-in-the-repertoire and antigen presentation (determinant selection) models of Ir gene control.

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Abbreviations

APC:

antigen-presenting cells

BSA:

bovine serum albumin

BSS:

Mishell-Dutton balanced salt solution

CFA:

complete Freund's adjuvant

CMI:

cell-mediated immunity

CY:

cyclophosphamide

DTH:

delayed-type hypersensitivity

GA:

poly(Glu60Ala40)

GAT:

poly (Glu60Ala30Tyr10)

GT:

poly(Glu50Tyr50)

GT-MBSA:

GT complexed to methylated bovine serum albumin

It:

immune response

LN:

lymph node

PPD:

purified protein derivative of tuberculin

TDH:

DTH T cells

Th:

helper T cells

Tprlf:

T-cell proliferation

Ts:

suppressor T cells

TsF:

T-cell suppressor factor(s)

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Authors and Affiliations

  1. The Department of Microbiology-Immunology, Northwestern University Medical School, 303 East Chicago Avenue, 60611, Chicago, Illinois

    Mary K. Kennedy, M. K. Jenkins & Stephen D. Miller

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  1. Mary K. Kennedy
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  2. M. K. Jenkins
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Kennedy, M.K., Jenkins, M.K. & Miller, S.D. Mechanisms of genetic control of immune responses. Immunogenetics 23, 292–301 (1986). https://doi.org/10.1007/BF00398791

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