EVIDENCE FOR THE STOCHASTIC ACQUISITION OF CYTOKINE PROFILE BY CD4(+) T-CELLS ACTIVATED IN A T-HELPER TYPE 2-LIKE RESPONSE IN-VIVO

Kelso, A; GROVES, P; TROUTT, AB; FRANCIS, K

Author(s): Kelso, A; GROVES, P; TROUTT, AB; FRANCIS, K;
Details: Publication Year 1995-05,Volume 25,Issue #5,Page 1168-1175
Journal Title: EUROPEAN JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: The diversity of cytokine production patterns displayed by T cells activated in vivo was investigated by analyzing short-term antigen-specific CD4(+) T cell clones and single CD4(+) T cells derived from draining lymph nodes of mice undergoing a Thelper 2 (Th2)-like response to keyhole limpet hemocyanin (KLH). On average, 2.7% of CD4(+) lymph node cells gave rise to clones in the presence of the immunizing antigen and, of these, about 90% secreted interleukin-4 (IL-4) and 20% secreted interferon-gamma (IFN-gamma) when restimulated after 2 weeks in vitro. Almost all IFN-gamma-producing clones co-produced IL-4. The definition of clones as positive or negative for cytokine synthesis depended on assay sensitivity, however, since their titers were distributed continuously from the threshold of detection over at least a 1000-fold range. Reverse-transcription polymerase chain reaction analysis of 59 clones revealed multiple patterns of co-expression of IL-2, IL-3, IL-4, IL-6, IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA. Although most clones contained detectable IL-4 and IL-6 mRNA and a minority contained IFN-gamma mRNA, only 1 clone expressed the canonical Th2 cytokine profile. The observed frequencies of mRNA co-expression for most of the six cytokines (including IL-4 with IFN-gamma), and the frequency of co-secretion of IL-4 and IFN-gamma, were not significantly different from those predicted for random association. Independent regulation of IL-4 and IFN-gamma mRNA expression was confirmed at the single-cell level in a polyclonal population of KLH-primed CD4(+) cells, among which co-expression of these cytokines again occurred at the frequency predicted for a random event. The data suggest that the polarization of this immune response towards a Th2 cytokine profile is achieved by altering the probabilities of expression of the IL-4, IFN-gamma and other cytokine genes at the population lever, rather than by selective expansion of a distinct T cell subset.
Publisher: VCH PUBLISHERS INC
Keywords: COLONY-STIMULATING FACTOR; VERSUS-HOST REACTION; INTERFERON-GAMMA; LYMPHOKINE ACTIVITIES; MURINE LEISHMANIASIS; SECRETING CD4+; LYMPHOCYTES-T; TH2 CELLS; IFN-GAMMA; CLONES
Publisher's Version: https://doi.org/10.1002/eji.1830250506
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1995-05-01 12:00:00