PMID- 8102390
OWN - NLM
STAT- MEDLINE
DCOM- 19930913
LR  - 20201215
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 178
IP  - 3
DP  - 1993 Sep 1
TI  - The natural immune response to inhaled soluble protein antigens involves major 
      histocompatibility complex (MHC) class I-restricted CD8+ T cell-mediated but MHC 
      class II-restricted CD4+ T cell-dependent immune deviation resulting in selective 
      suppression of immunoglobulin E production.
PG  - 889-99
AB  - The immunological basis for atopy is currently ascribed to an inherent bias in 
      the CD4+ T cell response to nonreplicating antigens presented at mucosal 
      surfaces, resulting in dominance of the T helper 2 (Th2) interleukin 4 
      (IL-4)-producing phenotype, which favors IgE production. In contrast, the 
      "normal" response to such antigens involves a predominance of interferon gamma 
      (IFN-gamma)-producing Th1 clones. This difference has been suggested to be the 
      result of active selection in atopics for Th2 (and hence against Th1) clones at 
      the time of initial antigen presentation. In the study below, we demonstrate that 
      the natural immune response to inhaled protein antigens, particularly in animals 
      expressing the low immunoglobulin E (IgE) responder phenotype, includes a major 
      histocompatibility complex (MHC) class I-restricted CD8+ T cell component, the 
      appearance of which is associated with active suppression of IgE antibody 
      production. Thus, continued exposure of rats to aerosolized ovalbumin (OVA) 
      antigen elicits a transient IgE response, that is terminated by the onset of a 
      state of apparent "tolerance" to further challenge, and this tolerant state is 
      transferable to naive animals with CD8+ T cells. Kinetic studies on in vitro T 
      cell reactivity in these aerosol-exposed rats demonstrated biphasic CD4+ Th2 
      responses which terminated, together with IgE antibody production, and coincident 
      with the appearance of MHC class I-restricted OVA-specific IFN-gamma-producing 
      CD8+ T cells. However, the latter were not autonomous in vitro and required a 
      source of exogenous IL-2 for initial activation, which in CD(8+)-enriched 
      splenocyte cultures could be provided by small numbers of contaminating 
      OVA-specific CD4+ T cells. This represents the first formal evidence for the 
      induction of an MHC class I-restricted T cell response to natural mucosal 
      exposure to an inert protein antigen, and is consistent with a growing literature 
      demonstrating sensitization of MHC class I-restricted CD8+ T cells by deliberate 
      immunization with soluble proteins. We suggest that crossregulation of MHC class 
      II-restricted CD4+ T cells via cytokine signals generated in parallel CD8+ T cell 
      responses represents a covert and potentially important selection pressure that 
      can shape the nature of host responses to nonreplicating antigens presented at 
      mucosal surfaces.
FAU - McMenamin, C
AU  - McMenamin C
AD  - Western Australian Research Institute for Child Health, Princess Margaret 
      Hospital, Perth.
FAU - Holt, P G
AU  - Holt PG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Aerosols)
RN  - 0 (CD8 Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin-2)
RN  - 0 (Proteins)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Aerosols
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8 Antigens/analysis
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Immunization
MH  - Immunization, Passive
MH  - Immunoglobulin E/*immunology
MH  - Immunoglobulin G/immunology
MH  - Interferon-gamma/metabolism
MH  - Interleukin-2/metabolism
MH  - Lymphocyte Activation
MH  - Major Histocompatibility Complex
MH  - Ovalbumin/chemistry/*immunology
MH  - Proteins/chemistry/*immunology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Solubility
MH  - T-Lymphocyte Subsets/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
PMC - PMC2191183
EDAT- 1993/09/01 00:00
MHDA- 1993/09/01 00:01
PMCR- 1994/03/01
CRDT- 1993/09/01 00:00
PHST- 1993/09/01 00:00 [pubmed]
PHST- 1993/09/01 00:01 [medline]
PHST- 1993/09/01 00:00 [entrez]
PHST- 1994/03/01 00:00 [pmc-release]
AID - 93353144 [pii]
AID - 10.1084/jem.178.3.889 [doi]
PST - ppublish
SO  - J Exp Med. 1993 Sep 1;178(3):889-99. doi: 10.1084/jem.178.3.889.