Skip to main content
menu
URMC / Microbiology & Immunology / Research / Xenopus Laevis / Models to Study / Ontogeny of the Immune System

 

Ontogeny of the Immune System

Immune systems

Fig.1: Two developmentally and physiologically distinct
immune systems coexist in the same species

Unlike mammals, the Xenopus immune system undergoes striking developmental changes twice during its life (Fig 1): first during embryogenesis, and then again during the metamorphosis (Flajnik al., 1987). The thymus, first colonized by embryonic stem cells a few days after fertilization, undergoes a second wave of stem cell immigration after losing about 90% of its lymphocytes during metamorphosis. The embryonic and larval periods of thymocyte differentiation take place in different environments, since during metamorphosis the whole organism is remodeled and many new proteins are expressed that could be considered antigenic by the larval immune system. The emerging adult lymphocytes, therefore, are likely to be subjected to a new education by the adult "self," resulting in a new balance of self-tolerance. Despite the drastic remodeling, a long lasting immunological memory persists through metamorphosis for B and T cell antigens.

Comparative Overview Of The Immune System Capacity Of Larval And Adult X. laevis

Thymus-dependent Functions

Immune System Characteristics Larva (Ancestral-like system) Adult (Mammalian-like system)
MLR Poor Better
CTL Not Demonstrated Yes (MHC-restricted)
IgM to IgY switch Poor Yes
Rejection of MHC identical but minor H-antigen disparate skin grafts Incomplete (tolerance) Acute
MHC classical class I Absent (cell surface and mRNA) Present
Non-classical class Ib No mRNA detected Present
CD8+ T-cell Present Present
MK cell and NK activity Present at late stages Present

Tumor Immunity

Immune System Characteristics Larva (Ancestral-like system) Adult (Mammalian-like system)
Tumor Ag recognition Yes Yes
Anti-tumor effector Weak Stronger
Hsp immunogenicity Yes but not peptide specific Yes, peptide-specific

X. laevis adults display an efficient immune system (Table 1) very similar to mammals (e.g. rearranging TCR and Ig genes, as well as MHC class I- and class II-restricted T cell recognition; Du Pasquier et al., 1989), whereas the larval presents some deficiencies such as a poor switch from IgM to IgY (Xenopus IgG functional equivalent), a specific tolerogenic rather than allodestructive response to minor histocompatibility antigens, and an inefficient anti-tumor effector system. Both MHC class I and class II genes are differentially regulated during metamorphosis. Consistent expression of class I does not occur until metamorphosis; class II expression is restricted in larvae to thymic epithelium, peripheral B and accessory cells. After metamorphosis, class II antigens are expressed constitutively on virtually all thymocytes and mature peripheral T- as well as B-cells. The MHC class I-deficient larva constitutes a naturally occurring "knockout".